Distinct Regions of the Haloferax volcanii Dolichol Phosphate-Mannose Synthase AglD Mediate the Assembly and Subsequent Processing of the Lipid-Linked Mannose

J Bacteriol. 2022 Jan 18;204(1):e0044721. doi: 10.1128/JB.00447-21. Epub 2021 Oct 11.

Abstract

Haloferax volcanii AglD is currently the only archaeal dolichol phosphate (DolP)-mannose synthase shown to participate in N-glycosylation. However, the relation between AglD and Pyrococcus furiosus PF0058, the only archaeal DolP-mannose synthase for which structural information is presently available, was unclear. In this report, similarities between the PF0058 and AglD catalytic domains were revealed. At the same time, AglD includes a transmembrane domain far longer than that of PF0058 or other DolP-mannose synthases. To determine whether this extension affords AglD functions in addition to generating mannose-charged DolP, a series of Hfx. volcanii strains expressing truncated versions of AglD was generated. Mass spectrometry revealed that a version of AglD comprising the catalytic domain and only two of the six to nine predicted membrane-spanning domains could mediate mannose addition to DolP. However, in cells expressing this or other truncated versions of AglD, mannose was not transferred from the lipid to the protein-bound tetrasaccharide precursor of the N-linked pentasaccharide normally decorating Hfx. volcanii glycoproteins. These results thus point to AglD as contributing to additional aspects of Hfx. volcanii N-glycosylation beyond charging DolP with mannose. Accordingly, the possibility that AglD, possibly in coordination with AglR, translocates DolP-mannose across the plasma membrane is discussed.

Keywords: Archaea; Haloferax volcanii; N-glycosylation; dolichol phosphate-mannose synthase.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Archaeal Proteins / genetics
  • Archaeal Proteins / metabolism*
  • Catalytic Domain
  • Dolichol Monophosphate Mannose / chemistry
  • Dolichol Monophosphate Mannose / metabolism*
  • Ethylenediamines
  • Gene Expression Regulation, Bacterial / physiology
  • Gene Expression Regulation, Enzymologic / physiology
  • Haloferax volcanii / enzymology*
  • Haloferax volcanii / genetics
  • Haloferax volcanii / metabolism
  • Mannosyltransferases / genetics
  • Mannosyltransferases / metabolism*
  • Phenols
  • Protein Conformation
  • Protein Domains

Substances

  • Archaeal Proteins
  • Ethylenediamines
  • Phenols
  • agidol AF-2
  • Dolichol Monophosphate Mannose
  • Mannosyltransferases
  • dolichyl-phosphate beta-D-mannosyltransferase